The latest medical research on Immunology & Allergy

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about immunology & allergy gathered by our medical AI research bot.

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Renal safety of tenofovir alafenamide vs tenofovir disoproxil fumarate: A pooled analysis of 26 clinical trials.

AIDS

Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with improvement in markers of renal dysfunction in individual randomised trials; however the comparative incidence of clinically significant renal events remains unclear.

We pooled clinical renal safety data across 26 treatment naïve and antiretroviral switch studies in order to compare the incidence of proximal renal tubulopathy (PRT) and discontinuation due to renal adverse events (AEs) between participants taking TAF-containing regimens versus those taking TDF-containing regimens. We performed secondary analyses from seven large randomised studies (two treatment-naïve and five switch studies) to compare incidence of renal AEs, treatment-emergent proteinuria, changes in serum creatinine, creatinine clearance, and urinary biomarkers (albumin, beta-2-microglobulin, and retinol binding protein to creatinine ratios).

Our integrated analysis included 9,322 adults and children with HIV (n = 6360 TAF, n = 2962 TDF) with exposure of 12,519 person-years to TAF and 5947 to TDF. There were no cases of PRT in participants receiving TAF versus 10 cases in those receiving TDF (p < 0.001), and fewer individuals on TAF (3/6360) versus TDF (14/2962) (p < 0.001) discontinued due to a renal AE. Participants initiating TAF- vs. TDF-based regimens had more favourable changes in renal biomarkers through 96 weeks of therapy.

These pooled data from 26 studies, with over 12,500 person-years of follow-up in children and adults, support the comparative renal safety of TAF over TDF.

Allogeneic stem cell transplantation in HIV-1 infected patients with high-risk hematological disorders.

AIDS

Although a number of patients with HIV infection and hematological disease have successfully undergone allogeneic hematopoietic stem cell transplantation (HSCT), short and long-term outcomes remain not well known. We report the largest Spanish experience treating HIV-infected adult patients with high-risk hematological malignancies with allogeneic HSCT.

We retrospectively reviewed 22 HIV-positive patients who received allogeneic HSCT in 5 centers in Spain.

22 patients with high-risk hematological malignancies were transplanted between 1999 and 2018. Median age was 44 years. With a median follow-up of 65 months (8-112), OS and EFS were 46%. NRM was 14% at 12 months and relapse was 24% at 24 months. Grade II-IV aGvHD rate was 40%, and moderate/severe cGvHD rate was 41% at 24 months. All patients received cART. Two patients showed severe toxicity related to drug interaction with anti-retroviral therapy. 68% of patients showed infectious complications with viral infections as the most frequent cause. Two patients had invasive aspergillosis and one patient presented disseminated tuberculosis. All survivors except one maintained undetectable HIV load at last follow-up after HSCT.

Allogeneic HSCT is an effective therapy for high-risk hematological malignancies in patients with HIV infection, and long-term HIV suppression with cART is feasible. However, drug interactions with anti-retroviral agents, occurrence of GVHD, and frequent infectious complications account for a complex procedure in this population. Selected HIV-infected patients with hematologic malignancies should be considered for allo-HSCT when indicated, in experienced centers.

Risk factors for antiretroviral therapy (ART) discontinuation in a large multinational trial of early ART initiators.

AIDS

We aimed to investigate potential causes of higher risk of treatment interruptions within the multi-country START trial in 2015.

We defined baseline as the date of starting ART and a treatment interruption as discontinuing ART for ≥2 weeks. Participants were stratified by randomisation arm and followed from baseline to earliest of end date of the initial phase of START, death, date of consent withdrawn, or date of first treatment interruption. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals for factors that may predict treatment interruptions in each arm.

Of the 3,438 participants who started ART, 2286 were in the immediate arm and 1152 in the deferred arm. 12.9% of people in the immediate arm and 10.5% of people in the deferred arm experienced ≥1 treatment interruption by 3 years after starting ART. In adjusted analyses, age (HR for 35-50 years: 0.75 (95% CI: 0.59, 0.97) and >50 years: 0.53 (0.33, 0.80) vs. < 35 years), education status (HR for post-graduate education vs. less than high-school education (0.23 (0.10, 0.50)) and region (HR for United States vs. Europe/Israel (3.16 (2.09, 4.77)) were significantly associated with treatment interruptions in the immediate arm. In the deferred arm, age and education status were significantly associated with treatment interruptions.

Within START, we identified younger age and lower educational attainment as potential causes of ART interruption. There is a need to strengthen adherence advice and wider social support in younger people and those of lower education status.

Acceptability and outcomes of distributing HIV self-tests for male partner testing in Kenyan maternal child health and family planning clinics.

AIDS

Providing HIV self-tests to women for distribution to male partners may provide a unique opportunity to increase male partner and couples testing among women in HIV high-burden settings.

Between November 2017 and June 2018, we offered self-tests for at-home couples or partner HIV-testing to HIV-uninfected women seeking routine maternal child health (MCH) and family planning (FP) services at 8 facilities in Kisumu, Kenya. Women accepting self-tests were offered ≥2 self-tests (OraQuick) to take to their partner(s) with instructions on use. HIV self-testing (HIVST) outcomes were evaluated using available programmatic data.

Overall, 3620 women were offered self-tests for at-home male partner HIV testing. The median age was 24 years (IQR 21-28) and 81% were in monogamous marriages. Overall, 1422 (39%) women reported having a partner of unknown HIV status, of whom 755 (53%) accepted self-tests. Among women with partners of unknown HIV status who declined self-tests (n=667), 49% reported needing to consult their partner. Pregnant women were more likely to accept HIVST than non-pregnant women (prevalence ratio = 1.2, 95%CI 1.0-1.4, p = 0.013). Self-testing outcomes were ascertained for 389 (44%) women who accepted self-tests. Among these women, 93% offered HIVSTs to their male partner; of these, 95% reported their male partners used the self-test and 99% used a self-test with their partner.

Among women attending routine MCH and FP services who had male partners of unknown HIV status, over half accepted self-tests for partner testing. Most women with outcomes ascertained reported that male partners accepted and used self-tests and that couples testing occurred.

Effects of 24 Week Toll-Like Receptor 9 Agonist Treatment in HIV-1+ Individuals: a single-arm, phase 1B/2A trial.

AIDS

Enhance immune function in HIV-1 infected individuals as a necessary step towards the goal of HIV-1 remission in the absence of combination antiretroviral therapy (cART).

TEACH: Toll-like receptor 9 Enhancement of Antiviral immunity in Chronic HIV-1 infection: a phase 1b/2a trial; ClinicalTrials.gov NCT02443935.

This exploratory, single-arm clinical trial tested the immune enhancement effects of 24-weeks of TLR9 agonist (MGN1703; Lefitolimod; 60 mg x2 weekly) therapy in 12 HIV-1 infected individuals on suppressive cART. Safety was assessed throughout the study. The primary outcome was reduction in total CD4+ T cell viral DNA levels. Secondary outcomes included safety, detailed immunological and virological analyses, and time to viral rebound (viral load >5000 copies/mL) after randomization into an analytical treatment interruption (ATI).

12 individuals completed the treatment phase and 9 completed the ATI. Adverse events were limited and consistent with previous reports for MGN1703. While the dosing regimen led to potent T cell activation and increased HIV-1-specific T cell responses, there were no cohort-wide changes in persistent virus (total CD4+ T cells viral DNA; p = 0.34). No difference in time to rebound was observed between the ATI arms (Log Rank p = 0.25). One of nine ATI participants, despite harboring a large replication-competent reservoir, controlled viremia for 150 days via both HIV-1-specific cellular and antibody-mediated immune responses.

24 weeks of MGN1703 treatment was safe and improved innate as well as HIV-1-specific adaptive immunity in HIV-1+ individuals. These findings support the incorporation of TLR9 agonism into combination HIV-1 cure strategies.

HIV stigma and viral load among African-American women receiving treatment for HIV: A longitudinal analysis.

AIDS

African-American women are more likely than other women in the United States to experience poor HIV-related health; HIV stigma may contribute to these outcomes. This study assessed the relationship between HIV stigma and viral load, over time, among a sample of African-American women receiving treatment for HIV, and explored social support and depressive symptoms as mediators.

Data came from a randomized trial of an intervention to reduce HIV stigma among African-American women in HIV care in Chicago, Illinois and Birmingham, Alabama. Sociodemographic and psychosocial data were collected at up to six study visits over 14 months. Viral loads were extracted from medical records during the study period. Generalized linear mixed effects models were used to estimate associations between overall, internalized, and enacted HIV stigma and viral load over time. Mediation analyses were used to estimate indirect effects via social support and depressive symptoms.

Data from 234 women were analyzed. Overall HIV stigma was significantly associated with subsequent viral load (adjusted β = 0.24, p = 0.005). Both between-subject (adjusted β = 0.74, p < 0.001) and within-subject (adjusted β = 0.34, p = 0.005) differences in enacted stigma were associated with viral load. Neither social support nor depressive symptoms were statistically significant mediators.

Ongoing experiences of HIV stigmatization may contribute to increased viral load among African-American women in primary HIV care. Interventions should aim to alleviate the consequences of stigma experienced by patients and prevent future stigmatization.

Health provider training is associated with improved engagement in HIV care among adolescents and young adults in kenya.

AIDS

Adolescents and young adults (AYA) have poorer retention, viral suppression, and survival than other age groups. We evaluated correlates of initial AYA engagement in HIV care at facilities participating in a randomized trial in Kenya.

Retrospective cohort study METHODS:: Electronic medical records from AYA ages 10-24 attending 24 HIV care facilities in Kenya were abstracted. Facility surveys assessed provider trainings and services. HIV provider surveys assessed AYA training and work experience. Engagement in care was defined as return for first follow-up visit within 3 months among newly enrolled or recently re-engaged (returning after >3 months out of care) AYA. Multi-level regression estimated risk ratios (RRs) and 95% Confidence Intervals (CIs), accounting for clustering by facility. Final models adjusted for AYA individual age and median AYA age and number enrolled per facility.

Among 3,662 AYA records at first eligible visit, most were female (75.1%), older (20-24 years: 54.5%), and on ART (79.5%). Overall, 2,639 AYA returned for care (72.1%) after enrollment or re-engagement visit. Engagement in care among AYA was significantly higher at facilities offering provider training in adolescent-friendly care (85.5% vs. 67.7%; aRR 1.11, 95%CI:1.01-1.22) and that used the Kenyan government's AYA care checklist (88.9% vs. 69.2%; aRR 1.14, 95%CI:1.06-1.23). Engagement was also significantly higher at facilities where providers reported being trained in AYA HIV care (aRR 1.56, 95%CI:1.13-2.16).

Adolescent-specific health provider training and tools may improve quality of care and subsequent AYA engagement. Health provider interventions are needed to achieve the '90-90'-90' targets for AYA.

The benefit of immediate compared to deferred ART on CD4+ Cell count recovery in early HIV infection.

AIDS

To assess the impact of immediate versus deferred antiretroviral therapy (ART) on CD4+ recovery among individuals early in HIV infection.

Three subgroups were defined: 1) infected ≤6 months (n = 373); 2) infected 6-24 months (n = 2,634); and 3) infected > 24 months (n = 1,605). Follow-up CD4+, CD8+, and CD4:CD8 ratio for the immediate and deferred ART groups were compared by subgroup using linear models. For the deferred ART group, decline to CD4+ <350 cells/μL or AIDS according to infection duration was compared using time-to-event methods.

Follow-up CD4+ count differences (immediate minus deferred) were greater for those recently infected (+231 cells/μL) compared to the two other subgroups (202 and 171 cells/μL; p<0.001). CD4:CD8 ratio treatment differences varied significantly (p<0.001) according to duration of infection. In the deferred ART group, decline to CD4+ < 350 cells/μL or AIDS was greater among those recently infected (16.1 versus 13.2 and 10.5 per 100 person years for those infected 6-24 and > 24 months; p = 0.002).

In this randomized comparison of immediate versus deferred ART, the CD4+ cell count difference was greatest for those recently infected with HIV, emphasizing the importance of immediate ART initiation.

Perinatal outcomes associated with maternal HIV and antiretroviral therapy in pregnancies with accurate gestational age in South Africa.

AIDS

To assess the association of maternal HIV infection and antiretroviral therapy (ART) with perinatal outcomes among women with accurate pregnancy dating and birth weights.

Gestational age was estimated by first-trimester ultrasound and birth weight was measured in a standardised manner within 24 hours of birth. The primary composite outcome "adverse perinatal outcome" included preterm birth, low birth weight, small for gestational age, stillbirth and neonatal death. Specific adverse perinatal outcomes were secondary outcomes. Logistic regression models adjusted for multiple confounders.

Of 633 women included in the analysis, 229 (36.2%) were HIV-positive and 404 (63.8%) HIV-negative. Among 125 HIV-positive women who provided detailed information on HIV and ART, 96.7% had clinical stage 1 of HIV disease and 98.4% were on ART during pregnancy, mostly WHO-recommended efavirenz-based ART. Among 109 HIV-positive women with information on timing of ART initiation, 38 (34.9%) initiated ART preconception and 71 (65.1%) antenatally. No newborns were HIV-positive. In univariable analysis, maternal HIV infection was associated with increased risk of the composite "adverse perinatal outcome" (OR 1.44; 95%CI 1.03, 2.03), neonatal death (OR 6.15; 95%CI 1.27, 29.88) and small for gestational age (OR 1.55; 95%CI 1.01, 2.37). After adjusting for confounders, maternal HIV infection remained associated with "adverse perinatal outcome" (adjusted OR (AOR)1.47; 95%CI 1.01, 2.14) and neonatal death (AOR 7.82; 95%CI 1.32, 46.42). No associations with timing of ART initiation were observed.

Despite high ART coverage, good maternal health, and very low vertical HIV transmission rate, maternal HIV infection remained associated with increased risk of adverse perinatal outcomes. Larger studies using first trimester ultrasound for pregnancy dating are needed to further assess associations with specific adverse perinatal outcomes.

HIV Incidence during breastfeeding and mother-to-child transmission in cape town, south africa.

AIDS

: Despite widespread concerns about HIV incidence in pregnant and postpartum women there are few data from Africa on HIV acquisition in breastfeedi...

Hearing complaints in HIV infection originate in the brain not the ear.

AIDS

Evidence suggests damage to brain auditory pathways, rather than inner ear damage, underlies the hearing difficulties HIV+ individuals report. But, anti-retroviral therapy (ART) may affect the hearing system and also lead to hearing complaints.

The ability to hear quiet sounds (pure-tone audiometry), cochlear outer hair cell function (distortion-product otoacoustic emissions (DPOAEs), and gaps-in-noise detection thresholds (a central auditory processing test) were assessed at each visit. Visits were scheduled for 6-month intervals, but the number and spacing of visits varied. In the group that started ART while in the study, 107 HIV+ individuals had audiometric thresholds, 98 had DPOAEs, and 98 had gap measurements suitable for analysis. Data were analyzed using a linear mixed model with time and starting ART as fixed effects and individual subject repeated measures as random effects.

Starting ART did not affect audiometric or gap detection thresholds. The slope of the DPOAE amplitude vs. time relationship was more negative after starting ART but did not differ from the HIV- group. Gap thresholds were higher in the HIV+ group.

ART did not affect audiometric thresholds significantly suggesting common ART drugs are not major ototoxins. The gap detection results from the study show effects on central auditory processing in HIV+ individuals, supporting the origin of HIV-related hearing complaints in the central auditory system.

Dimorphism in the T-cell receptor constant region affects T-cell function, phenotype and HIV outcome.

AIDS

CD8 T-cells recognize HLA-peptide complex through the T-cell receptor (TCR). Whilst amino acid variation in TCR variable chains often affects antigen specificity, dimorphism in the beta chain constant region (TRBC1 and TRBC2) is not thought to affect T-cell function. A recent study suggested that adoptive transfer of TRBC1-specific CAR-T cells provided an option for T-cell leukemia therapy that preserved T-cell immunity in the TRBC2 subset. This raises an important question as to whether TRBC1T cells are qualitatively different from TRBC2T cells.

Sixty-six antiretroviral therapy-naïve HIV-infected individuals, including 19 viraemic controllers and 47 non-controllers, were enrolled. Peripheral blood mononuclear cells were isolated for T-cell functional assays, tetramer analyses, TRBC1 staining and immunophenotyping.

Viraemic controllers had a higher proportion of circulating TRBC1T cells than non-controllers, raising the possibility that TRBC1T cells might be associated with HIV control. TRBC1T cells also showed more functional T-cell responses against both HIV and cytomegalovirus (p < 0.01). The immunophenotypes of TRBC1-bearing T cells were skewed towards naïve and central memory phenotypes, whereas the majority of TRBC2-expressing T cells were terminally differentiated. Inverse correlations were observed between %TRBC1T cells and HIV plasma viral load, which was most pronounced for CD8 T cells (r = -0.7096, p = 0.00002357).

These data suggest that TRBC1T-cell responses are of better quality than their TRBC2 counterparts, which should be considered in immunotherapeutic strategies for HIV infection. Conversely, depletion of TRBC1T cells as part of the treatment of TRBC1 T-cell malignancies may lead to compromised T-cell response quality.